Use of Low Dose Ketoconazole in Prostate Cancer That Does Not Respond to Hormone Therapy and Prior Chemotherapy

• ClinicalTrials.gov Identifier: NCT00895310
• Recruitment Status: Completed
• First Posted: May 8, 2009
• Results First Posted: February 15, 2017
• Last Update Posted: March 30, 2017
• Sponsor: University of California, Davis
• Information provided by (Responsible Party): University of California, Davis

Study Description

Brief Summary:

The purpose of this study is to test the safety of ketoconazole and how well it works after chemotherapy has been used. Ketoconazole at lower doses has been used for fungal infections however has not yet been approved by the Food and Drug Administration for use in prostate cancer. Ketoconazole has been used for many years at high doses for prostate cancer, and this study will be to look at use of lower dose ketoconazole after someone has received chemotherapy. Ketoconazole works by halting the production of steroids in your body, including testosterone, and is thought to work directly on prostate cancer cells in published lab studies.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Ketoconazole; Drug: Hydrocortisone	Phase 2

Detailed Description:

The aim of the study is to research the response of low dose ketoconazole in hormone refractory prostate cancer (HRPC) patients who have already undergone chemotherapy as part of their prostate cancer treatment. The hypothesis of the study is that HRPC patients who have been previously treated with chemotherapy will demonstrate objective PSA response rates to low dose ketoconazole, comparable to historical response rates reported in chemotherapy-naïve patients. This is a single arm trial, with all participants given ketoconazole 200mg TID, along with hydrocortisone given at 20mg in the morning, 10mg at night daily. Each cycle will consist of 28 days. The subject's study participation will continue until subject experiences disease progression, unacceptable toxicities, withdraws consent from the study or dies.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessing PSA Response in Low Dose Ketoconazole in Hormone Refractory Prostate Cancer Patients Who Have Failed at Least One Prior Systemic Chemotherapy Regimen
• Study Start Date: May 2009
• Actual Primary Completion Date: December 2014
• Actual Study Completion Date: May 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ketoconazole and Hydrocortisone; Ketoconazole 200mg PO TID + Hydrocortisone 20mg PO Qam, 10mg PO Qpm	Drug: Ketoconazole; Ketoconazole is taken three times a day by mouth.; Other Name: Nizoral; Drug: Hydrocortisone; Hydrocortisone is taken by mouth 20 mg every morning and 10 mg every evening.; Other Name: Cortef

Outcome Measures

Primary Outcome Measures :

1. Prostate Specific Antigen (PSA) Response (>50% Reduction From Baseline) [ Time Frame: From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years ]
   Percentage of patients who achieved a clinically significant decline in Prostate Specific Antigen (PSA) after initiation of ketoconazole therapy, defined as a >=50% decrease in PSA.

Secondary Outcome Measures :

1. PSA Response (>30% From Baseline) [ Time Frame: From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years ]
2. Progression Free Survival [ Time Frame: From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years ]
   Response Evaluation Criteria In Solid Tumors (RECIST) radiographic criteria for progression
3. Duration of Stable Disease [ Time Frame: From date of enrollment, every Cycle (4 weeks), until disease progression, unacceptable toxicities, study withdrawal, or death from any cause, whichever came first, assessed up to 2 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Patients must have histologically or cytologically proven prostate cancer with a Gleason score available or interpretable.
• Patients must have prostate cancer deemed to be hormone refractory, by progression of measurable or evaluable disease or rising PSA.
• Patients must be >18 years old
• Patients must have received at least one prior chemotherapy regimen >3 weeks prior to initiation of study and patients must have recovered from the side effects of the therapy
• Patients must have an ECOG status of 0-3
• Patients must have normal organ and marrow function, determined within 14 days of registration.
• Patients must have been surgically or medically castrated. If the method of castration was LHRH agonists (leuprolide or goserelin), then the patient must be willing to continue the use of LHRH agonists.
• Patients must have a serum total testosterone level <50 ng/dl
• If the patient has been treated with non-steroidal anti-androgens (flutamide, bicalutamide or nilutamide) or other hormonal treatment (megace or steroids), the patient must have stopped these agents at least 28 days prior to enrollment for flutamide, megace or steroids and at least 42 days prior to enrollment for bicalutamide or nilutamide; and the patients must have demonstrated progression of disease since the agents were suspended.

Exclusion Criteria:

• Patients with any condition that impairs the ability to swallow medications orally
• Patients who are unable to give informed consent
• Patients who have received ketoconazole treatment for prostate cancer in the past
• Patients with other active malignancies in the past 3 years except nonmelanoma skin cancer
• Patients may not be receiving any other investigational agents
• Patients with known hypersensitivity to ketoconazole
• Patients may not be taking certain medications, including terbinafine, astemizole, triazolam, statins (except pravastatin and fluvastatin) and acid suppressive agents (antacids, H2 blockers, PPI) while on ketoconazole, and patients on these medications must agree to discontinue these medications and consider alternative therapies.

Contacts and Locations

Locations

United States, California

University of California, Davis Cancer Center

Sacramento, California, United States, 95817

Sponsors and Collaborators

University of California, Davis

Investigators

• Principal Investigator: Primo N Lara Jr., MD; University of California, Davis Health System

More Information

Publications of Results:

Lo EN, Beckett LA, Pan CX, Robles D, Suga JM, Sands JM, Lara PN Jr. Prospective evaluation of low-dose ketoconazole plus hydrocortisone in docetaxel pre-treated castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis. 2015 Jun;18(2):144-8. doi: 10.1038/pcan.2015.2. Epub 2015 Feb 10.

• Responsible Party: University of California, Davis
• ClinicalTrials.gov Identifier: NCT00895310
• Other Study ID Numbers: 200916901; UCDCC#218 ( Other Identifier: University of California Davis )
• First Posted: May 8, 2009
• Results First Posted: February 15, 2017
• Last Update Posted: March 30, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by University of California, Davis:

PSA; Ketoconazole; Prostate Cancer; Hormone Refractory; Chemotherapy Regimen

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Prostatic Diseases; Ketoconazole; Hydrocortisone; Anti-Inflammatory Agents; Antifungal Agents; Anti-Infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Cytochrome P-450 CYP3A Inhibitors